As is known, the appropriately substituted 7-hydroxy-isoflavone-derivatives are suitable intermediates in the synthesis of 7-alkoxy-isoflavones which are effective medicines in human and veterinary therapy. Thus, it is desirable to prepare the 7-hydroxy-isoflavone-derivative of the formula (VII) in such chemical purity that it should be suitable for the preparation of the 7-alkylated end-product in appropriate purity, that is, it is an important requirement to suppress the formation of the contaminating derivatives of the formula (VI).
The 7-hydroxy-derivative of the formula (VII) can be prepared in the industry by subjecting the resorcinol-derivative of the formula (III) and an orthoformic acid ester of the general formula (IV) to ring closure. The following methods are known for carrying out the above synthesis:
In a pyridine-piperidine mixture by boiling for 1 hour (CA. 56, 2408) with a yield of 80% with 70% perchloric acid or POCl.sub.3 -dimethyl-formamide (Zsurn. Chem. Khim. 1970 40/2459; CA 75. 201219), with a yield of 33% using HCl as a catalyst (CA. 83, 193010), with a yield of 70%. In an analogous process the mixture is boiled for 8 hours in pyridine/piperidine mixture and unsubstituted isoflavone is prepared with a yield of 60% starting from 2-hydroxy-phenyl-benzyl-ketone (US-PS 3 340 276).
The mentioned ring closures are all performed at 110.degree.-150.degree. C. in the presence of a mixture of a solvent boiling at a temperature above 100.degree. C. (pyridine homologs, dimethyl-formamide etc ) and a secondary amine (piperidine, morpholine, pyrrolidine) preferably at the boiling point of &he mixture. In some cases the formed alcohol is distilled off during reaction, presumably in order to improve conversion or in order to raise temperature.
When reproducing said processes we have found that in addition to 7 hydroxy-isoflavone derivatives of the formula (VII) a significant amount& (in some cases 2-10% by weight measured by HPLC) of 7-ethoxy-isoflavone-derivative of the formula (VI) is formed among to other side products. By reducing the molar excess of ethyl-orthoformiate the yield is significantly reduced but the 7-ethoxy-isoflavone contamination cannot be eliminated. The 7-hydroxy-isoflavone-derivative of the formula (VII) prepared by this method can be purified only by an expensive me&hod using several solvent treatments.